The impact of the learning curve on adhesion

formation in a laparoscopic mouse model

Roberta Corona, M.D.,a Jasper Verguts, M.D.,a Maria Mercedes Binda, Ph.D.,a
Carlos Roger Molinas, M.D., Ph.D.,b Ron Schonman, M.D.,c and Philippe R. Koninckx, M.D., Ph.D.a
a
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven,
Belgium; b Neolife-Medicina y Cirugıa Reproductiva, Centro Medico La Costa, Asuncion, Paraguay; and c Department of
Obstetrics and Gynaecology, Sheba Medical Center, affiliated to Tel Aviv University, Tel Hashomer, Israel

Objective: To evaluate the impact of surgeon training on adhesion formation in a laparoscopic mouse model.
Laparoscopic surgery and bowel manipulation was demonstrated to enhance postoperative adhesion formation.
Design: Prospective randomized, controlled trial.
Setting: University laboratory research center.
Animal(s): 200 BALB/c and 200 Swiss female mice.
Intervention(s): Adhesions were induced by opposing bipolar lesions and 60 minutes of pneumoperitoneum. Each
surgeon operated on 80 mice (40 Swiss and 40 BALB/c), the only variable thus being his/her increasing experience.
Some surgeons were already experienced gynecologists, others were starting their training.
Main Outcome Measure(s): End points were the duration of surgery while performing the lesions. The adhesion
formation was scored quantitatively (proportion and total) and qualitatively (extent, type, and tenacity) after 7 days.
Result(s): With training, duration of surgery and adhesion formation decreased exponentially for all surgeons,
whether experienced or not. Experienced surgeons had initially a shorter duration of surgery, less adhesion forma-
tion, and less de novo adhesions than inexperienced surgeons.
Conclusion(s): These data suggest that laparoscopic skills improve with training, leading to a decrease in the du-
ration of surgery and formation of adhesions. Therefore completion of a standardized learning curve should be man-
datory when initiating adhesion formation studies both in laboratory or clinical setting. (Fertil Steril
2011;96:
193–7. 2011 by American Society for Reproductive Medicine.)
Key Words: Learning curve, laparoscopy, adhesions, mouse model, training, surgery

Surgical training has always been an essential part in the residency of
the young surgeon. Since the introduction of laparoscopic surgery,
learning curves are frequently used to analyze the effect of training
and to assess the competency of surgeons. This can be done, without
any risk for the patient (1), thanks to the development of different
methods of laparoscopic surgical training, such as live and cadaver
animal training, human cadaver training, box trainer, video trainer,
and virtual reality training by computer simulation (2). Learning
curves are different for different type of surgery and surgeons can
be experienced in one procedure and not in another (3–5).
Learning curves in endoscopic surgery, as reported in the litera-
ture, showed that they always improve outcomes in different surgi-
cal procedures (2, 6–11) and after a rapid improvement in skills at
the beginning, which varies with the skills investigated (tying,
suturing, cutting, dissecting, lifting, grasping, and transferring
objects with both hands) (12), a plateau is reached (i.e., knot tying
is learned much quicker than stitching) (13). Learning curves are re-
flected in a progressively decreasing operating time, an enhanced
precision, and a decrease in complications (6, 7, 14). Specifically,
the duration of surgery (14–19) and complication rate (18, 19) is
significantly lower for experienced surgeons compared with junior
ones (14), with an important impact on costs (20, 21).
The impact of learning curves on experiments involving animal
models has rarely been investigated (14). This might be especially
important in experiments investigating postoperative adhesion for-
mation, as adhesion formation has been shown to decrease with
a shorter duration of surgery (22) and with gentle tissue handling
(23, 24). Good surgical techniques is widely believed to decrease
postoperative adhesions.
During the past years our group developed and validated a strictly
standardized laparoscopic mouse model for the study of postopera-
tive adhesion formation and tumor implantation. To investigate the
minimum experience required to perform experiments we prospec-
tively investigated the learning curves and the impact of training on
the extent and the variability of postoperative adhesion formation, as
well as the effect on operating time.

Received January 24, 2011; revised and accepted April 15, 2011;
published online May 24, 2011.
R.C. has nothing to disclose. J.V. has nothing to disclose. M.M.B. has
nothing to disclose. C.R.M. has nothing to disclose. R.S. has nothing
to disclose. P.R.K. has nothing to disclose.
Supported by the Leuven Quality Surgery Fund (Fisher and Paykel Health-
care, Nordic Pharma, and eSaturnus NV).
Reprint requests: Roberta Corona, M.D., U.Z. Gasthuisberg, Department
of Obstetrics & Gynaecology, Herestraat 49, B3000 Leuven, Belgium
(E-mail: coronaroberta@gmail.com).
MATERIALS AND METHODS
The Laparoscopic Mouse Model for Adhesion Formation
The experimental setup (i.e., animals, anesthesia and ventilation,
laparoscopic surgery and induction, and scoring of peritoneal adhe-
sions) has been described in detail previously (22–31). Briefly, the
model consisted of performing bipolar lesions during laparoscopy
followed by 60 minutes of pure CO2 pneumoperitoneum. The
pneumoperitoneum was induced using the Thermoflator (Karl

0015-0282/$36.00 Fertility and Sterility Vol. 96, No. 1, July 2011 193
doi:10.1016/j.fertnstert.2011.04.057 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
Descargado para Anonymous User (n/a) en University of Rosario de ClinicalKey.es por Elsevier en septiembre 16, 2021. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
Storz) through a 2-mm endoscope with a 3.3 external sheath for
insufflation (Karl Storz) introduced into the abdominal cavity
through a midline incision caudal to the xyphoid appendix. The
incision was closed gas tight around the endoscope to avoid
leakage. The insufflation pressure was 15 mm Hg and humidified
gas (Humidifier 204320 33; Karl Storz) was used. After the
establishment of the pneumoperitoneum, two 14-gauge catheters
(Insyte-W, Vialon; Becton Dickinson) were inserted under
laparoscopic vision. Standardized 10-
1.6-mm lesions were
performed in the antimesenteric border of both right and left
uterine horns and in both the right and left pelvic side walls with
bipolar coagulation (20 W, standard coagulation mode, Autocon
350; Karl Storz). Because anesthesia and ventilation influence
body temperature (28), the timing between anesthesia (T0), intuba-
tion (at 10 minutes, T10), and the onset of the experiment (at 20 min-
utes, T20) was strictly controlled. After 7 days, adhesions were
scored quantitatively (proportion and total) and qualitatively (extent,
type, tenacity) blindly during laparotomy under a stereomicroscope.
The entire abdominal cavity was visualized using a xyphopubic
midline and a bilateral subcostal incision. After the evaluation of
ports sites and viscera (omentum, large and small bowels) for de
novo adhesions, the fat tissue surrounding the uterus was carefully
removed. The length of the visceral and parietal lesions and adhe-
sions were measured. Adhesions, when present, were carefully lysed
to evaluate their type and tenacity. The terminology of Pouly and
Seak-San (32) was used, describing de novo adhesion formation
for the adhesions formed at nonsurgical sites and adhesion forma-
tion for adhesions formed at the surgical site.
Animals
The present study was performed in 400, 12–13-week-old female
mice (i.e., 200 BALB/cJ@Rj mice; inbred strain) weighting 20–30
g and 200 Swiss mice (outbred strain) weighting 30–40 g. Animals
were kept under standard laboratory conditions and diet at the ani-
mal facilities of the Katholieke Universiteit Leuven. The study
was approved by the Institutional Review Animal Care Committee
of the Katholieke Universiteit Leuven.
Experimental Design and Surgical Procedures
The experiment was designed to evaluate the effect of training, as-
sessed by the consecutive surgeries, on operating time and on the ex-
tent and variability of postoperative adhesion formation. The
operating time was measured from T20 (i.e., from the beginning
of surgery, exactly 20 minutes after induction of anesthesia) until
the end of the procedure with the removal of catheters for instrumen-
tation and port sites closure. In addition, the codes of intervention
order were broken only at the end of the training experiment.
Each trainee performed sequentially 80 interventions to induce ad-
hesion formations. All trainees were inexperienced for the laparo-
scopic procedure in a mouse model, but some of them were
experienced gynecologists after their training in gynecology (3
trainees), whereas other surgeons were inexperienced at the end of
medical school (2 trainees).
All experiments were performed using block randomization by
days. Therefore, a block of animals comprising one animal of
each strain, one BALB/c mouse and one Swiss mouse were always
operated in a single session on the same day to avoid day-to-day var-
iability. In addition, within a block, experiments were performed in
random order. Before surgical procedure initial body temperature
and weight were measured.
194 Corona et al. Techniques and instrumentation
Descargado para Anonymous User (n/a) en University of Rosario de ClinicalKey.es por Elsevier en septiembre 16, 2021. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
FIGURE 1
Duration of surgery during training. Learning curve expressed as
duration of the surgery versus number of consecutive procedures
for experienced (n ¼ 3) and nonexperienced surgeons (n ¼ 2). Dots
represent the real operating times for each mouse. The lines were
calculated from the individual operating times after a two-phase
exponential decay model.
Corona. Techniques and instrumentation. Fertil Steril 2011.
Statistics
Statistical analyses were performed using GraphPad Prism version 4
(GraphPad Software Inc.). Multifactorial analyses were achieved
with GLM and Logistic procedures using the SAS System (SAS In-
stitute). The coefficient of variation (CV), a normalized measure of
dispersion, was calculated as the ratio of the standard deviation to
the mean multiplied by 100.
RESULTS
With training, assessed by consecutive surgeries, duration of surgery
decreased exponentially in both groups, demonstrating a clear learn-
ing curve that can be described as a two-phase exponential decay
model (nonexperienced: R2 ¼ 0.72; experienced: R2 ¼ 0.73)
(Fig. 1). In BALB/c mice the real and calculated operating times
for nonexperienced surgeons decreased from 19  6 minutes and
22  4 minutes for the first 10 procedures to 7  1 minutes and
7  1 minutes for the last 10 procedures (P¼.0001; P¼.0001,
respectively). For experienced surgeons time decreased from 8 
1 minutes and 10  3 minutes for the first 10 procedures to 4 
0.3 minutes and 4  0.03 minutes for the last 10 procedures. In
Swiss mice the real and calculated operating times from nonexper-
ienced surgeons decreased from 17  6 minutes and 22  4 minutes
for the first 10 procedures to 7  1 minutes and 7  1 minutes for the
last 10 procedures (P¼.0001; P¼.0001, respectively). For experi-
enced surgeons time decreased from 8  3 minutes and 10  3 min-
utes for the first 10 procedures to 4  0.3 minutes and 5  0.03
minutes for the last 10 procedures (P¼.0001; P¼.0001, respec-
tively). As expected, the real and calculated operating times both
for BALB/c and Swiss mice were not statistically different (t-test)
both for the first 10 procedures and for the last 10 procedures.
When the effects of training with time, the experience of the surgeon
and the mouse strain were evaluated simultaneously using multifac-
torial analysis (proc GLM), we confirmed the importance of de-
creasing operating time (P¼.0001) and the effect of experience
Vol. 96, No. 1, July 2011

FIGURE 2
Duration of the surgery and adhesion formation during learning
curve in different mouse strain. Duration of the surgery and
adhesion formation during learning curves in BALB/c (n ¼ 200) and
Swiss mice (n ¼ 200). Number of procedures were grouped by
groups of 10 blocks (1 block ¼ 2 procedures: 1 BALB/c þ 1 Swiss).
Mean and SD are indicated.
Corona. Techniques and instrumentation. Fertil Steril 2011.
(P¼.0001), whereas the mouse strain was not important as could be
anticipated (P¼not significant [NS]) (Fig. 2).
Similarly, the effects of training (expressed by the consecutive
number of surgeries), operating time, experience, and mouse strain
on adhesion formation were evaluated using multifactorial analysis
(proc GLM) (Figs. 2 and 3). Adhesion formation was lower with the
consecutive number of surgeries (proportion: P¼.01; total: P¼.01;
extension: P¼.02; type: P¼.01; tenacity: P¼006), for surgeries of
shorter operating time (proportion: P¼.02; total: P¼.04; extension:
P¼.02; type: P¼.02; tenacity: P¼.04), among experienced surgeons
FIGURE 3
Adhesion formation during learning curve. Adhesion formation
expressed as proportion of adhesions versus number of
consecutive procedures in both experienced (n ¼ 3) and
nonexperienced surgeons (n ¼ 2). Mean and SD are indicated.
Corona. Techniques and instrumentation. Fertil Steril 2011.
Fertility and Sterility
Descargado para Anonymous User (n/a) en University of Rosario de ClinicalKey.es por Elsevier en septiembre 16, 2021. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
(proportion: P<.0001; total: P¼.04; extension: P¼.001; type:
P¼.03; tenacity: P¼.04), and in Swiss mice (P¼NS) (Fig. 2).
It was decided arbitrarily to make four groups of 10 blocks (G1,
block 1–10; G2, block 11–20; G3, block 21–30; G4, block 31–40).
With this grouping, the interanimal variability for operating time
and for adhesion formation was assessed using the CV. The CV of
operating time among nonexperienced surgeons were 41%, 35%,
25%, and 20% for BALB/c mice and 39%, 40%, 22%, and 17%
for Swiss mice for G1, G2, G3, and G4, respectively; among expe-
rienced surgeons were 45%, 24%, 20%, and 22% for BALB/c mice
and 37%, 24%, 20%, and 21% for Swiss mice for G1, G2, G3, and
G4, respectively. The CV of the proportion of adhesions were 62%,
48%, 54%, and 38% for BALB/c mice and 106%, 92%, 96%, and
77% for Swiss mice for G1, G2, G3, and G4, respectively. The ef-
fects of the consecutive number of surgeries, measured by groups,
and of mouse strain on operating time and its CV and on the propor-
tion of adhesions and its CV were evaluated with a multifactorial
analysis (proc GLM). Both operating time and its CV decreased
with the number of surgeries (P¼.0001; P¼.0001, respectively),
whereas they were not affected by mouse strain (P¼NS; P¼NS, re-
spectively). Both the proportion of adhesions and its CV decreased
with the number of surgeries (P¼.002; P¼NS) and were affected by
mouse strain (i.e., for BALB/c mice the proportion of adhesions was
higher and the CV was lower).
DISCUSSION
To the best of our knowledge this is the first article aiming to
study the effect of surgical training on postoperative adhesion for-
mation in a laparoscopic mouse model. A previous study, performed
in rabbits, showed that postoperative adhesion formation, duration
of surgery, and complication rate decreased with surgeon training,
expressed by the consecutive number of procedures performed
(14, 33, 34).
In the present study, we compared two groups of surgeons (i.e.,
experienced and nonexperienced surgeons). Experienced surgeons
not only started with lower duration of surgery but also achieved
the plateau earlier (after 10 procedures), whereas nonexperienced
surgeons started with longer duration of surgery and, although the
duration decreased, it did not achieve the level of experienced sur-
geons even after 80 consecutive procedures. A less traumatic,
more precise and gentle surgical technique gained with experience
appears to be important as postoperative adhesion formation was
lower already after the first 10 procedures within the group of expe-
rienced surgeons in comparison with nonexperienced surgeons, con-
firming the data of the effect of manipulation-enhanced adhesions
(23). This difference among groups of surgeons decreased with
the number of surgical procedures, underlining the importance of
training. Our data confirm the well-known effect of training on the
learning curve (6, 12, 13, 22, 25–28, 30, 35, 36). Gentle tissue
handling, however, is more complex than is reflected in the
duration of surgery, as for similar operating times, experienced
surgeons had always less adhesions than inexperienced surgeons
during the entire learning curve.
Postoperative adhesion formation is influenced not only by surgi-
cal training but also by the duration of the pneumoperitoneum, which
in the present study was kept constant at 60 minutes. Less adhesion
formation with shorter procedures may happen due to less exposure
to CO2 pneumoperitoneum and thus to less pneumoperitoneum-
enhanced hypoxia, CO2, and pH changes. In the study performed
in rabbits, duration of surgery also seemed to be important in the out-
come of postoperative adhesion formation, although it is difficult to
195
completely separate both effects as duration of surgery and training
of surgeon are intimately related.
Other reports studying only the effect of CO2 or helium pneumo-
peritoneum on postoperative adhesion formation have shown an im-
portant effect of the time of exposure. Those studies show the same
situation—the longer the exposure, the higher the adhesion forma-
tion (22, 37).
Our study indicates that genetic background could also influence
adhesion formation, at least after laparoscopic surgery (38). BALB/c
mice, an inbred strain, showed lower interanimal variability and
higher adhesion formation (the latter not significant) in comparison
with Swiss mice, an outbred strain, observation to take into account
when developing a standardized animal model for the study of adhe-
sion formation. Strain differences have been reported for other pro-
cesses involving fibrosis and healing responses such as hepatic,
lung, and colorectal fibrosis (39–41), myocardial and ear wound
healing (42, 43), and bone regeneration (44). This is not surprising
because inbred strains, maintained by sibling (brother
sister) mat-
ing for 20 or more generations, are genetically almost identical,
homozygous at virtually all loci, and with high phenotypic unifor-
mity (45). This less interanimal variability in inbred strains
has been reported for many processes such as sleeping time under
anesthesia (46).
The mouse model has many advantages compared with other an-
imal models because it is relatively cheap, easy to handle, and does
not require strict sterile conditions for surgery. Furthermore, it is
particularly useful for diverse studies because of the availability of
animals with low genetic variability (i.e., inbred mice), underex-
pressing or overexpressing specific genes (i.e., transgenic mice),
and immunodeficient by spontaneous mutation (i.e., nude mice
[T-cell deficient] and SCID mice [T&B cell deficient]). In addition,
many specific mouse assays and monoclonal antibodies are
available.
In conclusion, first, this study confirms that surgical training is ex-
tremely important, not only in a hospital setting when dealing with
patients but also when performing surgical studies with the aim of
analyzing the outcome. In this case, training experience has a marked
effect on the development of postoperative adhesion formation. Sec-
ond, it is preferable to use a strain with high adhesion formation po-
tential and low interanimal variability such as BALB/c mice. We
believe fewer inbred animals will be needed to achieve a given level
of statistical precision than if outbred animals are used (44). It is,
however, necessary to point out that inbred strains in general weigh
less than outbred strains (average of 20 g vs. 32 g), which increases
the technical skills required to do the experiments, especially those
involving laparoscopic surgery.
Acknowledgments: The authors thank Mads Riiskjaer for participating in the
learning curve. We do thank Storz AG for their generous supply of
equipment.

REFERENCES
1. Moorthy K, Munz Y, Jiwanji M, Bann S, Chang A,
Darzi A. Validity and reliability of a virtual reality up-
per gastrointestinal simulator and cross validation us-
ing structured assessment of individual performance
with video playback. Surg Endoscop Other Intervent
Techn 2004;18:328–33.
2. Munz Y, Moorthy K, Bann S, Shah J, Ivanova S,
Darzi SA. Ceiling effect in technical skills of surgical
residents. Am J Surg 2004;188:294–300.
3. Herrell SD, Smith JA. Laparoscopic and robotic rad-
ical prostatectomy: what are the real advantages?
BJU Intern 2005;95:3–4.
4. Tekkis PP, Fazio VW, Lavery IC, Remzi FH,
Senagore AJ, Wu JS, et al. Evaluation of the learning
curve in heal pouch-anal anastomosis surgery. Ann
Surg 2005;241:262–8.
5. Tekkis PP, Senagore AJ, Delaney CP, Fazio VW.
Evaluation of the learning curve in laparoscopic
colorectal surgery—comparison of right-sided
and left-sided resections. Ann Surg
2005;242:83–91.
6. Aggarwal R, Tully A, Grantcharov T, Larsen CR,
Miskry T, Farthing A, et al. Virtual reality simulation
training can improve technical skills during laparo-
scopic salpingectomy for ectopic pregnancy. BJOG
2006;113:1382–7.
7. Aggarwal R, Black SA, Hance JR, Darzi A,
Cheshire NJ. Virtual reality simulation training can
improve inexperienced surgeons’ endovascular skills.
Eur J Vasc Endovasc Surg 2006;31:588–93.
8. Hyltander A, Liljegren E, Rhodin PH, Lonroth H. The
transfer of basic skills learned in a laparoscopic sim-
ulator to the operating room. Surg Endoscop Other
Intervent Techn 2002;16:1324–8.
9. Seymour NE, Gallagher AG, Roman SA,
O’Brien MK, Bansal VK, Andersen DK, et al. Virtual
reality training improves operating room perfor-
mance—results of a randomized, double-blinded
study. Ann Surg 2002;236:458–64.
10. Watterson JD, Beiko DT, Kuan JK, Denstedt JD. A
randomized, prospective blinded study validating
the acquisition of ureteroscopy skills using a computer
based virtual reality endourological simulator. J Urol
2002;168:1928–32.
11. Grantcharov TP, Kristiansen VB, Bendix J,
Bardram L, Rosenberg J, Funch-Jensen P. Random-
ized clinical trial of virtual reality simulation for
laparoscopic skills training. Br J Surg
2004;91:146–50.
12. Van Sickle KR, Ritter EM, Baghai M,
Goldenberg AE, Huang IP, Gallagher AG, et al.
Prospective, randomized, double-blind trial of
curriculum-based training for intracorporeal sutur-
ing and knot tying. J Am Coll Surg
2008;207:560–8.
13. Vossen C, Van Ballaer P, Shaw RW, Koninckx PR. Ef-
fect of training on endoscopic intracorporeal knot ty-
ing. Hum Reprod 1997;12:2658–63.
14. Molinas CR, Binda MM, Mailova K,
Koninckx PR. The rabbit nephrectomy model for
training in laparoscopic surgery. Hum Reprod
2004;19:185–90.
15. Shabtai M, Rosin D, Zmora O, Munz Y, Scarlat A,
Shabtai EL, et al. The impact of a resident’s se-
niority on operative time and length of hospital
stay for laparoscopic appendectomy—outcomes
used to measure the resident’s laparoscopic skills.
Surg Endoscop Other Intervent Techn
2004;18:1328–30.
16. Farnworth LR. A comparison of operative times in ar-
throscopic ACL reconstruction between orthopaedic
faculty and residents: the financial impact of ortho-
paedic surgical training in the operating room. Iowa
Orthoped J 2001;21:31–5.
17. Babineau TJ, Becker J, Gibbons G, Sentovich S,
Hess D, Robertson S, et al. The ‘‘cost’’ of operative
training for surgical residents. Arch Surg 2004;
139:366–9.
18. Kauvar DS, Braswell A, Brown BD, Harnisch M. In-
fluence of resident and attending surgeon seniority on
operative performance in laparoscopic cholecystec-
tomy. J Surg Res 2006;132:159–63.
19. Wilkiemeyer M, Pappas TN, Giobbie-Hurder A,
Itani KMF, Jonasson O, Neumayer LA. Does resident
post graduate year influence the outcomes of inguinal
hernia repair? Ann Surg 2005;241:879–82.
20. Barth RJ, Babineau, Hiebert C, Deckers PJ,
Russell PS, Goldfarb WB, et al. The ‘‘cost’’ of opera-
tive training for surgical residents—discussion. Arch
Surg 2004;139:369–70.
21. Bridges M, Diamond DL. The financial impact of
teaching surgical residents in the operating room.
Am J Surg 1999;177:28–32.
22. Molinas CR, Mynbaev O, Pauwels A, Novak P,
Koninckx PR. Peritoneal mesothelial hypoxia during
pneumoperitoneum is a cofactor in adhesion forma-
tion in a laparoscopic mouse model. Fertil Steril
2001;76:560–7.
23. Schonman R, Corona R, Bastidas A, De Cicco C,
Koninckx PR. Effect of upper abdomen tissue manip-
ulation on adhesion formation between injured areas
in a laparoscopic mouse model. J Min Invas Gynecol
2009;16:307–12.
24. Corona R, Verguts J, Schonman R, Binda MM,
Mailova K, Koninckx PR. Post-operative inflamma-
tion at the abdominal cavity increases adhesion for-
mation in a laparoscopic mouse model. Fertil Steril
2011;95:1224–8.
25. Molinas CR, Campo R, Elkelani OA, Binda MM,
Carmeliet P, Koninckx PR. Role of hypoxia inducible
factors 1alpha and 2alpha in basal adhesion formation
and in carbon dioxide pneumoperitoneum-enhanced
adhesion formation after laparoscopic surgery in trans-
genic mice. Fertil Steril 2003;80(Suppl 2):795–802.
26. Molinas CR, Elkelani O, Campo R, Luttun A,
Carmeliet P, Koninckx PR. Role of the plasminogen
system in basal adhesion formation and carbon diox-
ide pneumoperitoneum-enhanced adhesion formation
after laparoscopic surgery in transgenic mice. Fertil
Steril 2003;80:184–92.
27. Molinas CR, Campo R, Dewerchin M, Eriksson U,
Carmeliet P, Koninckx PR. Role of vascular endothe-
lial growth factor and placental growth factor in basal

196 Corona et al. Techniques and instrumentation Vol. 96, No. 1, July 2011

Descargado para Anonymous User (n/a) en University of Rosario de ClinicalKey.es por Elsevier en septiembre 16, 2021. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
 adhesion formation and in carbon dioxide
pneumoperitoneum-enhanced adhesion formation af-
ter laparoscopic surgery in transgenic mice. Fertil
Steril 2003;80(Suppl 2):803–11.
28. Binda MM, Molinas CR, Mailova K, Koninckx PR.
Effect of temperature upon adhesion formation in
a laparoscopic mouse model. Hum Reprod 2004.
29. Elkelani OA, Binda MM, Molinas CR, Koninckx PR. Ef-
fect of adding more than 3% oxygen to carbon dioxide
pneumoperitoneum on adhesion formation in a laparo-
scopic mouse model. Fertil Steril 2004;82:1616–22.
30. Elkelani OA, Molinas CR, Mynbaev O, Koninckx PR.
Prevention of adhesions with crystalloids during lap-
aroscopic surgery in mice. J Am Assoc Gynecol Lap-
arosc 2002;9:447–52.
31. Binda MM, Molinas CR, Hansen P, Koninckx PR. Ef-
fect of desiccation and temperature during laparos-
copy on adhesion formation in mice. Fertil Steril
2006;86:166–75.
32. Pouly JL, Seak-San S. Adhesions: laparoscopy versus
laparotomy. In: diZerega GS, editor. Peritoneal sur-
gery. New York: Springer; 2000. p. 183–92.
33. Molinas CR, Cabral CR, Koninckx PR. Effect of the
diameter of the endoscope and of surgeon training
on the duration and quality of laparoscopic surgery
in a rabbit model. J Am Assoc Gynecol Laparosc
1999;6:447–52.
Fertility and Sterility
Descargado para Anonymous User (n/a) en University of Rosario de ClinicalKey.es por Elsevier en septiembre 16, 2021. Para uso
personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
34. Ordonez JL, Dominguez J, Evrard V, Koninckx PR.
The effect of training and duration of surgery on ad-
hesion formation in the rabbit model. Hum Reprod
1997;12:2654–7.
35. Aggarwal R, Darzi A. Technical-skills training in the
21st century. N Engl J Med 2006;355:2695–6.
36. Aggarwal R, Mytton OT, Derbrew M, Hananel D,
Heydenburg M, Issenberg B, et al. Training and sim-
ulation for patient safety. Qual Saf Health Care
2010;19(Suppl 2):i34–43.
37. Baba Y, Uetsuka K, Nakayama H, Dot K. Rat strain
differences in the early stage of porcine-serum-
induced hepatic fibrosis. Exp Toxicol Pathol
2004;55:325–30.
38. Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W,
Flavell RA, et al. Adenosine metabolism and murine-
strain-specific IL-4-induced inflammation, emphy-
sema, and fibrosis. J Clin Invest 2006;116:1274–83.
39. Skwarchuk MW, Travis EL. Murine strain differences
in the volume effect and incidence of radiation-
induced colorectal obstruction. Intern J Radiation On-
col Biol Physics 1998;41:889–95.
40. Osadchii O, Norton G, Deftereos D, Woodiwiss A.
Rat strain-related differences in myocardial adrener-
gic tone and the impact on cardiac fibrosis, adrenergic
responsiveness and myocardial structure and func-
tion. Pharmacol Res 2007;55:287–94.
41. Caldwell RL, Opalenik SR, Davidson JM, Caprioli RM,
Nanney LB. Tissue profiling MALDI mass spectrometry
reveals prominent calcium-binding proteins in the pro-
teome of regenerative MRL mouse wounds. Wound Re-
pair Regen 2008;16:442–9.
42. Mitchell CA, Grounds MD, Papadimitriou JM. The
genotype of bone-marrow-derived inflammatory cells
does not account for differences in skeletal-muscle re-
generation between Sjl/J and Balb/C mice. Cell Tis-
sue Res 1995;280:407–13.
43. McClearn GE, Hofer SM. Genes as gerontological
variables: uniform genotypes. Neurobiol Aging
1999;20:95–104.
44. Homanics GE, Le NQ, Kist F, Mihalek R, Hart AR,
Quinlan JJ. Ethanol tolerance and withdrawal re-
sponses in GABA(A) receptor alpha 6 subunit
null allele mice and in inbred C57BL/6J and strain
129/SvJ mice. Alcohol Clin Exper Res 1998;
22:259–65.
45. Molinas CR, Koninckx PR. Hypoxaemia induced by
CO(2) or helium pneumoperitoneum is a co-factor
in adhesion formation in rabbits. Hum Reprod
2000;15:1758–63.
46. Molinas CR, Binda MM, Campo R, Koninckx PR.
Adhesion formation and interanimal variability in
a laparoscopic mouse model varies with strains. Fertil
Steril 2005;83:1871–4.
197